4-chlorobutoxymethylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(4-Benzyloxybutyl)-4-piperidone is prepared from 4-piperidone and 1-chloro-4-benzyloxybutane essentially as described above in Example 38, Scheme C, step a.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(4-Benzyloxybutyl)-4-piperidone is prepared from 4-piperidone and 1-chloro-4-benzyloxybutane essentially as described above in Example 38, Scheme C, step a.

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an atmosphere of nitrogen, the Grignard reagent is prepared from 1-chloro-4-benzyloxybutane (39.7 g, 0.2 mol), magnesium turnings (10 g, 0.4 mol), and dry ether (400 ml). The Grignard solution is separated from the excess of magnesium, transferred to a 2 l flask, and cooled to -40° C. A solution of fluoroacetonitrile (10.6 g, 0.18 mol) in ether (100 ml) is added slowly, the temperature being maintained between -40° and -30° C. Stirring is continued for 30 minutes more at this temperature. The reaction mixture is then poured into a vigorously stirred solution of sodium cyanide (39 g) and ammonium chloride (59 g) in water (200 ml) containing some ice (200 g). The mixture is vigorously stirred and allowed to warm up to room temperature during one hour. The organic phase is separated and extracted with 1 N HCl (2×250 ml). Basification with concentrated ammonia, extraction with ether, drying, and evaporation gives the title compound as a brown oil (28.3 g). The Grignard solution is separated from the excess of magnesium transferred to a 2 l flask the temperature being maintained between -40° and -30° C The mixture is vigorously stirred to warm up to room temperature during one hour The organic phase is separated extracted with 1 N HCl (2×250 ml) Basification with concentrated ammonia, extraction with ether drying evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-benzyloxybutanol (64.8 g, 0.36 mol) in dry pyridine (200 ml) is stirred and heated to 50°-60° C. A solution of thionyl chloride (43 g, 0.36 mol) in pyridine (100 ml) is added slowly, and the mixture is kept at 60° C. for one more hour. After cooling to room temperature, the reaction mixture is poured into a mixture of ice and 2 N HCl. The mixture is saturated with sodium chloride, extracted with ether, and washed successively with water, 10% sodium bicarbonate, and water. Evaporation of solvent gives a yellow oil (49.7 g) which is distilled under vacuum to give the pure title compound (47 g), bp0.03-0.05 85°-90° C. heated to 50°-60° C is kept at 60° C. for one more hour extracted with ether washed successively with water, 10% sodium bicarbonate, and water Evaporation of solvent

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an atmosphere of nitrogen, the Grignard reagent is prepared from 1-chloro-4-benzyloxybutane (39.7 g, 0.2 mol), magnesium turnings (10 g, 0.4 mol), and dry ether (400 ml). The Grignard solution is separated from the excess of magnesium, transferred to a 2 l flask, and cooled to -40° C. A solution of fluoroacetonitrile (10.6 g, 0.18 mol) in ether (100 ml) is added slowly, the temperature being maintained between -40° and -30° C. Stirring is continued for 30 minutes more at this temperature. The reaction mixture is then poured into a vigorously stirred solution of sodium cyanide (39 g) and ammonium chloride (59 g) in water (200 ml) containing some ice (200 g). The mixture is vigorously stirred and allowed to warm up to room temperature during one hour. The organic phase is separated and extracted with 1N HCl (2×250 ml). Basification with concentrated ammonia, extraction with ether, drying, and evaporation gives 2-fluoromethyl-2-amino-6-benzyloxyhexanenitrile as a brown oil (28.3 g). The Grignard solution is separated from the excess of magnesium transferred to a 2 l flask the temperature being maintained between -40° and -30° C The mixture is vigorously stirred to warm up to room temperature during one hour The organic phase is separated extracted with 1N HCl (2×250 ml) Basification with concentrated ammonia, extraction with ether drying evaporation

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an atmosphere of nitrogen, the Grignard reagent is prepared from 1-chloro-4-benzyloxybutane (39.7 g, 0.2 mol), magnesium turnings (10 g, 0.4 mol), and dry ether (400 ml). The Grignard solution is separated from the excess of magnesium, transferred to a 2 l flask, and cooled to -40° C. A solution of fluoroacetonitrile (10.6 g, 0.18 mol) in ether (100 ml) is added slowly, the temperature being maintained between -40° and -30° C. Stirring is continued for 30 minutes more at this temperature. The reaction mixture is then poured into a vigorously stirred solution of sodium cyanide (39 g) and ammonium chloride (59 g) in water (200 ml) containing some ice (200 g). The mixture is vigorously stirred and allowed to warm up to room temperature during one hour. The organic phase is separated and extracted with 1N HCl (2×250 ml). Basification with concentrated ammonia, extraction with ether, drying, and evaporation gives 2-fluoromethyl-2-amino-6-benzyloxyhexanenitrile as a brown oil (28.3 g). The Grignard solution is separated from the excess of magnesium transferred to a 2 l flask the temperature being maintained between -40° and -30° C The mixture is vigorously stirred to warm up to room temperature during one hour The organic phase is separated extracted with 1N HCl (2×250 ml) Basification with concentrated ammonia, extraction with ether drying evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(4-Benzyloxybutyl)-4-piperidone is prepared from 4-piperidone and 1-chloro-4-benzyloxybutane essentially as described above in Example 38, Scheme C, step a.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(4-Benzyloxybutyl)-4-piperidone is prepared from 4-piperidone and 1-chloro-4-benzyloxybutane essentially as described above in Example 38, Scheme C, step a.